IFNAR2 p.Leu69=
c.207G>A · rs753111606 · VCV2086139
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0101%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 3.1, phastCons 0.92 |
| Overall | ||
| CADD | 4.045 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0101%
European (non-Finnish) · 119/1,175,922 alleles
Filtering AF
0.00862%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00806%
Overall
0.00833%
134/1,609,400 alleles · ultra-rare
exomes 121/1,457,252 · genomes 13/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0101% | 9,882 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,386 |
| African / African-American | 0.00401% | 24,943 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,570 |
| Admixed American | 0.00333% | 29,986 |
| South Asian | 0.0033% | 30,317 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- IFNAR2
- Protein
- p.Leu69=
- Coding
- c.207G>A
- MANE Select
- NM_001289125
- dbSNP
- rs753111606
- Type
- single nucleotide variant
- Location
- chr21:33245060 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.86 · 9 PDB
- Residue 69
- a β-strand
Similar variants
- IFNAR2 c.840+1G>T Uncertain significance ★★ same type
- IFNAR2 p.Arg397Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Arg90Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asn146Ser Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asn281Tyr Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asp198Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asp437Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Glu184Lys Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ifnar2-p-leu69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown